Prostate cancer is the most commonly occurring tumor in men. It is an adenocarcinoma that is second only to lung cancer in mortality. Prostate cancer currently accounts for about 35000 deaths each year in the United States alone. The incidence increases with age, and because there is an increasing number of men who are older than 50 years, when prostate cancer is often first diagnosed, the total number of cases increases yearly. Data compiled from the Centers for Disease Control National Center for Health Statistics report an alarming increase in the incidence of the disease since 1980 in the US. Carter, et al., estimated that during the next 8 to 10 years, prostate cancer cases will increase by 90%, and deaths from prostate cancer will increase by 37%; Prostate 1990;16:39-48.
Localized treatment with surgery and/or radiotherapy are curative in many patients whose disease is diagnosed early. However, up to 40% of patients with advanced disease, and a large proportion of all patients, eventually develop metastatic disease following localized therapy. Treatment for advanced disease initially involves hormonal manipulations and palliative radiotherapy. These strategies have proven to be of marked clinical benefit in terms of symptomatic relief, but have not resulted in long-term disease-free survival. The use of cytotoxic agents in the management of hormone-resistant advanced prostate cancer remains poorly defined. A few single agents have become "standard therapy", although demonstration of their efficacy, by contemporary standards, is lacking.
Combination chemotherapy is frequently employed, although its contribution to overall patient management is largely unsubstantiated, especially when critical assessment of efficacy parameters are used. Newer approaches using chemohormonal therapy and hormonal priming therapies have failed. High-dose chemotherapy with transplant regimens are not well-tolerated in an elderly population, to which most men suffering from prostate cancer belong. A growth factor inhibitor, suramin, has shown promising initial results. However, no therapy to date has been demonstrated to improve overall survival in patients with advanced hormone refractory prostate cancer.
Accordingly, a strong need continues to find new agents that can be utilized to treat prostate cancer. We have now discovered that 5-[(2-aminoethyl)amino]-2-[2-diethylamino)ethyl]-2H-[1]benzothiopyrano-[4, 3,2-cd]indazol-8-ol is effective clinically to treat prostate cancer. The compound, and its pharmaceutically acceptable salts, will be referred to herein as BTPI, referring to benzothiopyranoindazol.
BTPI is disclosed in U.S. Pat. No. 4,604,390. The compound is one of a large group of indazoles which are said to have antibacterial, antifungal, and antineoplastic activities. Data is present in the patent showing in vitro activity against L1210 and P388 murine leukemia cell lines. Because few oncolytic agents are effective in treating prostate cancer, and because in vitro activity against murine leukemia cell lines is not predictive of activity against prostate cancer, it is surprising that BTPI is clinically efficacious against prostate cancer.
An object of this invention is, therefore, to provide a new treatment for prostate cancer utilizing BTPI.